Abstract

It has been hypothesized that one mechanism contributing to the developmental toxicity of some xenobiotics is an embryonic/fetal zinc (Zn) deficiency that occurs secondary to toxicant-induced changes in maternal Zn metabolism. We studied the influence of diverse toxicants (urethane, ethanol, melphalan, arsenic, and α-hederin) on maternal-embryonic Zn metabolism and maternal liver metallothionein (MT) induction in Sprague-Dawley rats given a 65Zn-labelled meal by gavage 8 h after toxicant exposure and killed 10 h later on gestation day 12.5. Exposure to the toxicants resulted in increases in maternal hepatic MT concentrations that generally exceeded that which could be accounted for by reductions in food intake. 65Zinc retention was higher in maternal liver and lower in the products of conception in the toxicant-exposed groups. Strong linear relationships were found; as maternal liver MT concentrations increased, 65Zn retention in maternal liver was increased and 65Zn distribution to the conceptuses was decreased. These results support the hypothesis that diverse insults can produce developmental toxicity, in part, by altering maternal and embryonic Zn metabolism.

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